Increased bone density in mice lacking the proton receptor OGR1

Area of Science:

• Skeletal Biology
• Bone Physiology
• Acid-Base Balance

Background:

• Chronic metabolic acidosis can lead to bone resorption.
• Osteoblasts, bone-forming cells, express the proton-sensing G-protein-coupled receptor OGR1.
• OGR1 activation by protons triggers intracellular calcium signaling, potentially mediating acidosis-induced bone changes.

Purpose of the Study:

• To investigate the role of OGR1 in proton-induced bone resorption.
• To determine the effect of OGR1 deficiency on bone mass and turnover in vivo.

Main Methods:

• Utilized OGR1 knockout (OGR1(-/-)) and wild-type (C57/Bl6) mice.
• Assessed bone mineral density using micro-computed tomography.
• Evaluated bone histomorphometry, including osteoblast and osteoclast indices, in tibiae and vertebrae.

Main Results:

• OGR1(-/-) mice exhibited normal skeletal development without gross abnormalities.
• Increased trabecular and cortical bone volume was observed in OGR1(-/-) mice.
• Higher osteoblast numbers, enhanced bone formation rates, and increased osteoclast populations were noted in OGR1(-/-) mice, indicating increased bone turnover with a net gain in bone mass.

Conclusions:

• The absence of OGR1 results in increased bone mass in rapidly growing mice.
• Bone turnover is elevated in OGR1(-/-) mice, with bone formation exceeding resorption.
• These findings highlight the critical role of the proton receptor OGR1 in mediating bone's response to protons and maintaining skeletal homeostasis.